Molecular mechanism of Indian Hedgehog signalling in human sebocytes

The hedgehog signalling pathway plays a crucial role during regulation of hair cycle and homeostasis of mammalian skin. Furthermore, misregulation of this pathway is attributed to a range of skin diseases and cancers. In previous studies Indian hedgehog was identified to be the only Hedgehog ligand expressed in sebaceous glands. Moreover, modulation of hedgehog pathway activity was shown to affect size and number of sebaceous glands in the skin. Thereby, local inactivation of the canonical Wnt pathway seems to be prerequisite for correct sebaceous gland development. However, the underlying molecular mechanism has not been clarified, yet. Therefore, we hypothesise that Indian hedgehog signalling regulates proliferation and/or differentiation in human sebocytes. Thereby, activation of Hedgehog pathway and inactivation of canonical Wnt signalling might be cross-linked. To test this, we applied the human sebocyte cell line SZ95 as in vitro model by comparing three distinct sebocyte populations depending on their differentiation state: “undifferentiated”, “differentiating” and “terminally differentiated” after induction by arachidonic acid treatment. Terminally differentiated sebocytes displayed increased expression of IHH without endogenous pathway activation. In contrast, undifferentiated sebocyte displayed increased proliferation rate upon pathway activation by GLI1 and GLI2 expression. Additionally, our findings point to a role of the lipid metabolism in regulating these processes as shown by modulation of gene expression by addition of arachidonic acid. Importantly, overexpression of GLI1, GLI2 and GLI3 also revealed that each GLI transcription factors preferentially activates a distinct set of established and potentially new Hedgehog target genes in human sebocytes. Additionally, we identified a new mechanism of mutual regulation between Hedgehog and Wnt pathways on protein level in human sebocytes. More precisely, overexpression of GLI3 and GLI2 transcription factors resulted in accumulation of non-phosphorylated, active β-CATENIN, although Wnt pathway activity was not increased. Conversely, augmented levels of β-CATENIN in combination with GLI1 activator dramatically increased Gli reporter activity. In summary, we propose the following model where undifferentiated sebocytes are the target cells of Hedgehog signals originating from mature sebocytes and GLI repressors might block endogenous Wnt pathway by interference with β-CATENIN

Gold Nanoparticle-Based Surface-Enhanced Raman Scattering for Noninvasive Molecular Probing of Embryonic Stem Cell Differentiation

This study reports the use of gold nanoparticle-based surface-enhanced Raman scattering (SERS) for probing the differentiation of mouse embryonic stem (mES) cells, including undifferentiated single cells, embryoid bodies (EBs), and terminally differentiated cardiomyocytes. Gold nanoparticles (GNPs) were successfully delivered into all 3 mES cell differentiation stages without affecting cell viability or proliferation. Transmission electron microscopy (TEM) confirmed the localization of GNPs inside the following cell organelles: mitochondria, secondary lysosome, and endoplasmic reticulum. Using bright- and dark-field imaging, the bright scattering of GNPs and nanoaggregates in all 3 ES cell differentiation stages could be visualized. EB (an early differentiation stage) and terminally differentiated cardiomyocytes both showed SERS peaks specific to metabolic activity in the mitochondria and to protein translation (amide I, amide II, and amide III peaks). These peaks have been rarely identified in undifferentiated single ES cells. Spatiotemporal changes observed in the SERS spectra from terminally differentiated cardiomyocyte tissues revealed local and dynamic molecular interactions as well as transformations during ES cell differentiation

Progress in cross-border co-operation

Marguerite Deliege-Sequaris deals with the tax aspects of cross-national mergers, legislated by the 3rd Directive of the EEC. She pays especial attention to the instinctive impact of the Community Legislation for the protection of employees under the relative member state's worker participation laws.

Sorption of a branched nonylphenol and perfluorooctanoic acid on Yangtze River sediments and their model components

Many metabolites of organic surfactants such as nonylphenol (NP) and perfluorooctanoic acid (PFOA) are ubiquitously found in the environment and are toxic if not sorbed on soils and sediments. In this study, we quantified the sorption of the NP isomer with the highest endocrine activity, [4-(1-ethyl-1,3-dimethylpentyl) phenol] (NP111), and that of PFOA on Yangtze River sediments and its model components illite, goethite and natural organic matter. The sorption experiments were performed with (14)C-labeled NP111 and PFOA by batch or dialysis techniques. The results showed that the sorption isotherms of NP111 and PFOA on the sediments were fitted well by the linear adsorption model. The sorption of NP111 depended largely on the organic carbon content of the sediments. The K(OC) values of NP111 ranged from 6 × 10(3) to 1.1 × 10(4) L kg(-1) indicating that hydrophobic interaction between NP and organic carbon is the main mechanism of sorption. The sorption of NP111 on illite was poor. The sorption of PFOA on the sediments was significantly lower than that of NP111. The affinity of PFOA to adsorb on goethite was slightly higher than on the sediments, but was moderate on illite and negligible on a reference natural organic matter. Principal axis component analysis confirmed that various sediment parameters control the binding of PFOA. This analysis grouped the respective K(d) values to the contents of black carbon, iron oxides and clay, and, hence, to the specific surface area of the sediments

La genèse des distrbutions de volume et de densité des plaquettes

peer reviewedA discussion by 28 authors of the factors determining platelet heterogeneity in man and mammalsPlatelet heterogeneit

Inverse determination of heterotrophic soil respiration response to temperature and water content under field conditions

Heterotrophic soil respiration is an important flux within the global carbon cycle. Exact knowledge of the response functions for soil temperature and soil water content is crucial for a reliable prediction of soil carbon turnover. The classical statistical approach for the in situ determination of the temperature response (Q(10) or activation energy) of field soil respiration has been criticised for neglecting confounding factors, such as spatial and temporal changes in soil water content and soil organic matter. The aim of this paper is to evaluate an alternative method to estimate the temperature and soil water content response of heterotrophic soil respiration. The new method relies on inverse parameter estimation using a 1-dimensional CO2 transport and carbon turnover model. Inversion results showed that different formulations of the temperature response function resulted in estimated response factors that hardly deviated over the entire range of soil water content and for temperature below 25A degrees C. For higher temperatures, the temperature response was highly uncertain due to the infrequent occurrence of soil temperatures above 25A degrees C. The temperature sensitivity obtained using inverse modelling was within the range of temperature sensitivities estimated from statistical processing of the data. It was concluded that inverse parameter estimation is a promising tool for the determination of the temperature and soil water content response of soil respiration. Future synthetic model studies should investigate to what extent the inverse modelling approach can disentangle confounding factors that typically affect statistical estimates of the sensitivity of soil respiration to temperature and soil water content